Infectious disease screening system

ABSTRACT

An infectious disease screening system ( 1 ) for screening for infectious diseases, such as COVID-19 disease. The system comprises an ultrasonic transducer ( 49 ) for generating ultrasonic waves to lyse cells in a biological sample. The system ( 1 ) comprises a controller which controls the ultrasonic transducer ( 49 ) to oscillate at an optimum frequency for cell lysis, a PCR apparatus ( 16 ) which receives and amplifies the DNA from the sample; and a detection apparatus ( 70 ) which detects the presence of an infectious disease in the amplified DNA and provides an output which is indicative of whether or not the detection arrangement ( 70 ) detects the presence of an infectious disease in the amplified DNA.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 17/334,461, filed May 28, 2021, which is pending; which claimsthe benefit of and priority to European patent application no.20177685.3, filed on 1 Jun. 2020; European patent application no.20200852.0, filed on 8 Oct. 2020; European patent application no.20214228.7, filed on 15 Dec. 2020; and International patent applicationno. PCT/GB2021/050822, filed on 1 Apr. 2021, all of which areincorporated by reference herein in theft entirety.

FIELD

The present invention relates to an infectious disease screening systemfor screening for infectious diseases including, but not limited to,COVID-19 disease. The present invention more particularly relates toinfectious disease screening systems for screening for viral infectionsusing a Polymerase Chain Reaction (PCR) process including, but notlimited to, the screening for SARS-CoV-2 viral infections.

BACKGROUND

Technological advancements in the medical field have improved theefficiency of diagnostic methods and devices. Testing times have reduceddrastically, while ensuring reliable results. There are various testingmethods to test for infections of all types. To test for viralinfections, PCR (Polymerase Chain Reaction) is proven to be the mostreliable method. As with other methods, PCR has evolved to be moretime-efficient and cost-effective, while maintaining high standards ofreliability.

PCR is a technique that uses the two matching strands in DNA to amplifya targeted DNA sequence from just a few samples to billions of copies,which are then analyzed using Gel Electrophoresis, which separates DNAsamples according to their size.

Conventional Polymerase Chain Reaction (PCR):

A complete conventional PCR test comprises 3 or 4 steps as describedbelow:

1. Cell Lysis and Nucleic Acid (DNA/RNA) Extraction:

Once a patient sample is collected, either from the nose (nasopharyngealswab) or the throat (oropharyngeal swab), the sample is mixed with theelution buffer. The eluted solution is then filtered to remove any largeparticles (hair, skin fragments etc.). The filtered solution is pouredinto a lysing chamber.

Cell lysis is then performed to break or rupture the lipid bilayer ofthe cells in the sample to provide a gateway through which cell'scomponents, including DNA/RNA, are extracted.

Cell lysis is performed either chemically or electromechanically, or acombination of both. The process extracts the components and thesolution is filtered to separate the nucleic acids (DNA/RNA) from othercell components. The DNA/RNA is then ready for the next step.

2. Reverse Transcription (RT):

This step is only required if the nucleic acid is RNA and not DNA. Theprocess involves introducing an enzyme, known as reverse transcriptase,to the PCR solution containing the RNA to create a complementary DNA(cDNA) sequence from the RNA at a temperature between 40-50° C. Thereverse transcription step would precede any PCR related action sincePCR requires DNA or cDNA.

3. Polymerase Chain Reaction (PCR)

The principle of PCR is same regardless of the type of DNA sample. PCRrequires five core ingredients to be processed: the DNA sample, primers,DNA nucleotide bases, a polymerase enzyme, and a buffer solution toensure appropriate conditions for the reaction.

The PCR involves a process of heating and cooling known as thermalcycling. The thermal cycling has three steps: Denaturation, Annealing,and Extension.

Denaturation starts with heating the reaction solution to 95° C.-100° C.The high temperature is required for separation of the double-strandedDNA or cDNA into single strands.

Annealing is the binding of primers to the denatured strands of sampleDNA or cDNA. This process requires a temperature of 55° C.-62° C. Oncethe temperature is reached, it initiates the annealing stage in whichthe primers attach to the single strands.

Once the primers are attached, the temperature is raised to around 72°C. for the polymerase to attach and extend the primers along the lengthof the single strand to make a new double-stranded DNA.

To achieve optimal results, the thermal cycle is repeated ˜20-40 times,depending on the number of base pairs required for the test, andensuring that the desired temperature is achieved at each stage.

4. Gel Electrophoresis

After PCR has been completed, a method known as electrophoresis can beused to check the quantity and size of the DNA fragments produced. DNAis negatively charged and, to separate it by size, the PCR-processedsample is placed in an agarose gel with a current running through thegel that pulls the negatively charged DNA to the opposite end. Largerpieces of DNA encounter more resistance in the solution and therefore donot move as far as smaller segments over the same period of time.

The distance the DNA fragments travel, when compared to a known sample,gives the result of the test. During solution preparation, before thegel electrophoresis step, a fluorescent dye is added in order to see thebands of DNA and based on their location the length of the DNA is known.

Rapid PCR:

Rapid PCR is performed using shorter thermal cycle times (20-60 secondsper cycle) than conventional PCR to reduce overall test times. Rapid PCRalso uses real-time PCR, an automated rapid thermocycling process thatincorporates amplification and detection in a single process inside aclosed reaction vessel. This process significantly reduces the risk ofcontamination. Rapid PCR uses Fluorescence spectroscopy for detectionsimultaneously with the PCR's thermal cycles.

Rapid RT-PCR incorporates another process in the overall test whentesting for viruses (RNA). The additional process is the ReverseTranscription used to create cDNA from the RNA prior to the PCR processas described above.

Fluorescence Spectroscopy:

Fluorescence spectroscopy is used as an alternative to GelElectrophoresis to reduce overall duration of the test. Fluorescencespectroscopy uses light to excite the electrons in molecules of certaincompounds and causes them to emit light. That light is detected by adetector for fluorescence measurement which can be used foridentification of molecule(s) or changes in the molecule.

A global virus outbreak of the SARS-CoV-2 virus (COVID-19 disease),classed as a pandemic has sky-rocketed the demand for virus test kits.The demand also requires tests to be performed more quickly thanconventional tests that typically take 4-8 hours to complete, or evenrapid tests that take more than 2 hours to give results.

Conventional virus testing methods are usually performed for largequantities of samples and processed simultaneously. However, the longduration for each step, majorly PCR, increases wait-time for results.The rapid-PCR technique provides some lead time over the conventionalPCR by reducing the thermal cycle time, shortening the overall test timeto around 1-2 hours. However, even this test time is too long for usefulmass rapid screening for infectious diseases, such as COVID-19.

There is a need for improved systems and devices for infectious diseasescreening which alleviate at least some of the problems outlined herein.

SUMMARY

A COVID-19 disease screening system of some arrangements comprises: asonication chamber configured to receive a biological sample to bescreened for COVID-19 disease; an ultrasonic transducer which outputsultrasonic waves in a frequency range of approximately 2800 kHz toapproximately 3200 kHz to lyse cells from the biological sample withinthe sonication chamber; a controller comprising: an AC driver whichgenerates an AC drive signal at a predetermined frequency within thefrequency range of approximately 2800 kHz to approximately 3200 kHz andoutputs the AC drive signal to drive the ultrasonic transducer; anactive power monitor which monitors active power used by the ultrasonictransducer when the ultrasonic transducer is driven by the AC drivesignal, wherein the active power monitor provides a monitoring signalwhich is indicative of the active power used by the ultrasonictransducer; a processor which controls the AC driver and receives themonitoring signal from the active power monitor; and a memory storinginstructions which, when executed by the processor, cause the processorto:

-   -   A. control the AC driver to output the AC drive signal to the        ultrasonic transducer at a predetermined sweep frequency;    -   B. calculate the active power being used by the ultrasonic        transducer based on the monitoring signal;    -   C. control the AC driver to modulate the AC drive signal to        maximize the active power being used by the ultrasonic        transducer;    -   D. store a record in the memory of the maximum active power used        by the ultrasonic transducer and the sweep frequency of the AC        drive signal;    -   E. repeat steps A-D for a predetermined number of iterations        with the sweep frequency incrementing with each iteration such        that, after the predetermined number of iterations has occurred,        the sweep frequency has been incremented from a start sweep        frequency to an end sweep frequency;    -   F. identify from the records stored in the memory an optimum        frequency for the AC drive signal which is the sweep frequency        of the AC drive signal at which the maximum active power is used        by the ultrasonic transducer; and    -   G. control the AC driver to output the AC drive signal to the        ultrasonic transducer at the optimum frequency; wherein the        system further comprises: a Polymerase Chain Reaction, “PCR”,        apparatus which receives and amplifies DNA from lysed cells of        the biological sample; and a SARS-CoV-2 virus detection        apparatus which detects a presence of the SARS-CoV-2 virus that        causes COVID-19 disease in the amplified DNA and provides an        output which is indicative of whether or not the SARS-CoV-2        virus detection apparatus detects the presence of the COVID-19        disease in the amplified DNA.

In some arrangements, the active power monitor comprises: a currentsensor which senses a drive current of the AC drive signal driving theultrasonic transducer, wherein the active power monitor provides amonitoring signal which is indicative of the sensed drive current.

In some arrangements, the memory stores instructions which, whenexecuted by the processor, cause the processor to: repeat steps A-D withthe sweep frequency being incremented from a start sweep frequency of2800 kHz to an end sweep frequency of 3200 kHz.

In some arrangements, the memory stores instructions which, whenexecuted by the processor, cause the processor to: in step G, controlthe AC driver to output the AC drive signal to the ultrasonic transducerat a frequency which is shifted by between 1-10% of the optimumfrequency.

In some arrangements, the AC driver modulates the AC drive signal bypulse width modulation to maximize the active power being used by theultrasonic transducer.

In some arrangements, the memory stores instructions which, whenexecuted by the processor, cause the processor to: control the AC driverto alternately output the AC drive signal to the ultrasonic transducerat the optimum frequency for a first predetermined length of time and tonot output the AC drive signal to the ultrasonic transducer for a secondpredetermined length of time.

In some arrangements, the memory stores instructions which, whenexecuted by the processor, cause the processor to: alternately outputthe AC drive signal and to not output the AC drive signal according toan operating mode selected from:

First Second predetermined predetermined Operating length of time lengthof time mode (seconds) (seconds) 1 4 2 2 3 2 3 2 2 4 1 2 5 1 1 6 2 1 7 31 8 4 1 9 4 3 10 3 3 11 2 3 12 1 3

In some arrangements, the system further comprises: a heating apparatusincorporating: a heating recess which receives a part of the PCRapparatus; a moveable support element; a first heating element which iscarried by the support element; a second heating element which iscarried by the support element at a spaced apart position from the firstheating element, wherein the support element is moveable between a firstposition in which the first heating element is positioned closer to theheating recess than the second heating element and a second position inwhich the second heating element is positioned closer to the heatingrecess than the first heating element; and a motor which is configuredto move the support element cyclically between the first position andthe second position.

In some arrangements, the heating apparatus comprises: a temperaturesensor which senses the temperature of a liquid within the PCR apparatuspositioned within the heating recess, wherein the controller controlsthe movement of the first and second heating elements in response to thesensed temperature.

In some arrangements, the controller controls the first heating elementto heat a liquid within the PCR apparatus to substantially 45° C. duringa reverse transcriptase process.

In some arrangements, during a PCR process, the controller: controls thefirst heating element to heat a liquid within the PCR apparatus tosubstantially 55° C., controls the second heating element to heat aliquid within the PCR apparatus to substantially 95° C., and moves thesupport element cyclically between the first and second positions suchthat the first and second heating elements control the temperature of aliquid within the PCR apparatus to cycle between substantially 55° C.and substantially 95° C.

In some arrangements, the system further comprises: a moveable flow pathwhich is moveable to selectively provide a fluid flow path between asample chamber, the sonication chamber or a PCR chamber so that at leastpart of the sample can be transferred successively between the samplechamber, the sonication chamber and the PCR chamber.

In some arrangements, the system further comprises: a filtrationarrangement which filters fluid flowing out from the moveable flow path,the filtration arrangement comprising a first filter element which isprovided with pores of between 2 μm and 30 μm in diameter.

In some arrangements, the filtration arrangement comprises a secondfilter element which is superimposed on the first filter element, thesecond filter element being provided with pores of between 0.1 μm and 5μm in diameter.

A COVID-19 disease screening method of some arrangements comprises:placing a biological sample to be screened for COVID-19 disease into asonication chamber, the sonication chamber comprising an ultrasonictransducer which outputs ultrasonic waves in a frequency range ofapproximately 2800 kHz to approximately 3200 kHz to lyse cells from abiological sample within the sonication chamber; generating, by an ACdriver, an AC drive signal at a predetermined frequency within thefrequency range of approximately 2800 kHz to approximately 3200 kHz andoutputting the AC drive signal to the ultrasonic transducer to drive theultrasonic transducer; monitoring, by an active power monitor, activepower used by the ultrasonic transducer when the ultrasonic transduceris driven by the AC drive signal, wherein the active power monitorprovides a monitoring signal which is indicative of the active powerused by the ultrasonic transducer; and receiving, at a processor, themonitoring signal from the active power monitor; wherein the methodfurther comprises:

-   -   A. controlling, by the processor, the AC driver to output the AC        drive signal to the ultrasonic transducer at a predetermined        sweep frequency;    -   B. calculating, by the processor, the active power being used by        the ultrasonic transducer based on the monitoring signal;    -   C. controlling, by the processor, the AC driver to modulate the        AC drive signal to maximize the active power being used by the        ultrasonic transducer;    -   D. storing, by the processor, a record in the memory of the        maximum active power used by the ultrasonic transducer and the        sweep frequency of the AC drive signal;    -   E. repeating steps A-D for a predetermined number of iterations        with the sweep frequency incrementing with each iteration such        that, after the predetermined number of iterations has occurred,        the sweep frequency has been incremented from a start sweep        frequency to an end sweep frequency;    -   F. identifying, by the processor, from the records stored in the        memory the optimum frequency for the AC drive signal which is        the sweep frequency of the AC drive signal at which the maximum        active power is used by the ultrasonic transducer; and    -   G. controlling, by the processor, the AC driver to output the AC        drive signal to the ultrasonic transducer at the optimum        frequency;    -   wherein the method further comprises: receiving and amplifying        DNA from lysed cells of the biological sample at a Polymerase        Chain Reaction, “PCR”, apparatus; detecting, at a SARS-CoV-2        virus detection apparatus, a presence of the SARS-CoV-2 virus        that causes COVID-19 disease in the amplified DNA; and providing        an output which is indicative of whether or not the SARS-CoV-2        virus detection apparatus detects the presence of the COVID-19        disease in the amplified DNA.

In some arrangements, the method further comprises: sensing, by acurrent sensor, a drive current of the AC drive signal driving theultrasonic transducer; and providing, by the active power monitor, amonitoring signal which is indicative of the sensed drive current.

In some arrangements, the method further comprises: modulating, by theAC driver, the AC drive signal by pulse width modulation to maximize theactive power being used by the ultrasonic transducer.

In some arrangements, the method further comprises: controlling the ACdriver to alternately output the AC drive signal to the ultrasonictransducer at the optimum frequency for a first predetermined length oftime and to not output the AC drive signal to the ultrasonic transducerfor a second predetermined length of time.

In some arrangements, the method further comprises: controlling the ACdriver to alternately output the AC drive signal and to not output theAC drive signal according to an operating mode selected from:

First Second predetermined predetermined Operating length of time lengthof time mode (seconds) (seconds) 1 4 2 2 3 2 3 2 2 4 1 2 5 1 1 6 2 1 7 31 8 4 1 9 4 3 10 3 3 11 2 3 12 1 3

An infectious disease screening system of some arrangements comprises: asonication chamber configured to receive a biological sample to bescreened for an infectious disease; an ultrasonic transducer whichoutputs ultrasonic waves in a frequency range of approximately 2800 kHzto approximately 3200 kHz to lyse cells from the biological samplewithin the sonication chamber; a controller comprising: an AC driverwhich generates an AC drive signal at a predetermined frequency withinthe frequency range of approximately 2800 kHz to approximately 3200 kHzand outputs the AC drive signal to drive the ultrasonic transducer; anactive power monitor which monitors active power used by the ultrasonictransducer when the ultrasonic transducer is driven by the AC drivesignal, wherein the active power monitor provides a monitoring signalwhich is indicative of the active power used by the ultrasonictransducer; a processor which controls the AC driver and receives themonitoring signal from the active power monitor; and a memory storinginstructions which, when executed by the processor, cause the processorto:

-   -   A. control the AC driver to output the AC drive signal to the        ultrasonic transducer at a predetermined sweep frequency;    -   B. calculate the active power being used by the ultrasonic        transducer based on the monitoring signal;    -   C. control the AC driver to modulate the AC drive signal to        maximize the active power being used by the ultrasonic        transducer;    -   D. store a record in the memory of the maximum active power used        by the ultrasonic transducer and the sweep frequency of the AC        drive signal;    -   E. repeat steps A-D for a predetermined number of iterations        with the sweep frequency incrementing with each iteration such        that, after the predetermined number of iterations has occurred,        the sweep frequency has been incremented from a start sweep        frequency to an end sweep frequency;    -   F. identify from the records stored in the memory an optimum        frequency for the AC drive signal which is the sweep frequency        of the AC drive signal at which the maximum active power is used        by the ultrasonic transducer; and    -   G. control the AC driver to output the AC drive signal to the        ultrasonic transducer at the optimum frequency;    -   wherein the system further comprises: a Polymerase Chain        Reaction. “PCR”, apparatus which receives and amplifies DNA from        lysed cells of the biological sample; and an infectious disease        detection apparatus which detects a presence of an infectious        disease in the amplified DNA and provides an output which is        indicative of whether or not the infectious disease detection        apparatus detects the presence of an infectious disease in the        amplified DNA.

BRIEF DESCRIPTION OF THE DRAWINGS

So that the present invention may be more readily understood,embodiments of the present invention will now be described, by way ofexample, with reference to the accompanying drawings, in which:

FIG. 1 is a perspective schematic view of a system of some arrangementswith an assay device of some arrangements,

FIG. 2 is a schematic drawing of an assay device of some arrangements,

FIG. 3 is a schematic drawing of part of a system of some arrangementswith an assay device of some arrangements,

FIG. 4 is a perspective schematic view of part of an assay device ofsome arrangements,

FIG. 5 is a side view of the part of the assay device shown in FIG. 4,

FIG. 6 is an end view of the part of the assay device shown in FIG. 4,

FIG. 7 is a schematic drawing of part of an assay device of somearrangements,

FIG. 8 is a cross-sectional view of the part of the assay device shownin FIG. 7,

FIG. 9 is a cross-sectional view of the part of the assay device shownin FIG. 7,

FIG. 10 is a schematic diagram of the components of a filtrationarrangement of some arrangements,

FIG. 11 is a schematic drawing of part of an assay device of somearrangements,

FIG. 12 is schematic diagram showing a piezoelectric transducer modelledas an RLC circuit,

FIG. 13 is graph of frequency versus log impedance of an RLC circuit,

FIG. 14 is graph of frequency versus log impedance showing inductive andcapacitive regions of operation of a piezoelectric transducer,

FIG. 15 is flow diagram showing the operation of a controller of somearrangements,

FIG. 16 is a perspective view of part of an assay device of somearrangements,

FIG. 17 is a perspective view of part of an assay device of somearrangements,

FIG. 18 is a perspective view of part of an assay device of somearrangements,

FIG. 19 is a side view of the part of the assay device shown in FIG. 18,

FIG. 20 is an end view of the part of the assay device shown in FIG. 18,

FIG. 21 is a cross-sectional view of part of a system of somearrangements and part of an assay device of some arrangements,

FIG. 22 is a perspective view of part of a system of some arrangementsand part of an assay device of some arrangements,

FIG. 23 is a side view of part of an assay device of some arrangements,and

FIG. 24 is a perspective view of part of a system of some arrangements.

DETAILED DESCRIPTION

Aspects of the present disclosure are best understood from the followingdetailed description when read with the accompanying figures. It isnoted that, in accordance with the standard practice in the industry,various features are not drawn to scale. In fact, the dimensions of thevarious features may be arbitrarily increased or reduced for clarity ofdiscussion.

The following disclosure provides many different embodiments, orexamples, for implementing different features of the provided subjectmatter. Specific examples of components, concentrations, applicationsand arrangements are described below to simplify the present disclosure.These are, of course, merely examples and are not intended to belimiting. For example, the attachment of a first feature and a secondfeature in the description that follows may include embodiments in whichthe first feature and the second feature are attached in direct contact,and may also include embodiments in which additional features may bepositioned between the first feature and the second feature, such thatthe first feature and the second feature may not be in direct contact.In addition, the present disclosure may repeat reference numerals and/orletters in the various examples. This repetition is for the purpose ofsimplicity and clarity and does not in itself dictate a relationshipbetween the various embodiments and/or configurations discussed.

The following disclosure describes representative arrangements orexamples. Each example may be considered to be an embodiment and anyreference to an “arrangement” or an “example” may be changed to“embodiment” in the present disclosure. This disclosure establishesimproved aspects of a rapid result diagnostic assay system designed forpoint of care (POC) and/or home use for infectious disease screening,specifically SARS-COV-2 known to cause COVID-19 disease.

The assay devices and systems of some arrangements are for screening anyother infectious disease caused by pathogens, such as bacteria orviruses. In some arrangements, the assay devices and systems are forscreening for an infectious agent or disease selected from a groupincluding, but not limited to, influenza, coronavirus, measles, HIV,hepatitis, meningitis, tuberculosis, Epstein-Barr virus (glandularfever), yellow fever, malaria, norovirus, zika virus infection oranthrax.

In some arrangements, the assay devices and systems are for screening atarget sample in the form of a saliva sample, a sputum sample or a bloodsample. In other arrangements, the assay devices and systems are forscreening a target sample which is collected from a user by anasopharyngeal swab or an oropharyngeal swab.

The assay system of some arrangements comprises 13 main components: anassay device or pod containing various liquid chambers, a plungercolumn, a flow directing cog, a sonication chamber, a filtration array,a PCR fin, PCR reagents, a PCR method, a thermal cycler, an infectiousdisease detection apparatus, a lid, a method for reporting results, anda housing that contains all necessary parts to manipulate the pod.

Referring to FIG. 1 of the accompanying drawings, a system 1 forinfectious disease screening is configured for use with a removableassay device 2 which, in this arrangement, is in the form of asingle-use pod. In some arrangements, the system 1 is providedseparately from the assay device 2. In other arrangements, the system 1is provided in combination with the assay device 2. In furtherarrangements, the assay device 2 is provided without the system 1 butfor use with the system 1.

The system 1 comprises a housing 3 which houses the various componentsof the system 1. In this arrangement, the housing 3 comprises an opening4 which is closed by a door 5. The door 5 is configured to move betweenan open position, as shown in FIG. 1 and a closed position in which thedoor 5 closes the opening 4 in the housing 3. In this arrangement, thedoor 5 is provided with a handle 6 to facilitate opening and closing bya user. In this arrangement, the door 5 is provided to enable a user toopen the system 1 to insert the assay device 2 into the system 1, asindicated generally by arrow 7 in FIG. 1. Other arrangements incorporatea different access means to permit a user to insert the assay device 2into the system 1.

In this arrangement, the system 1 is a portable system. The housing 3 iscompact to enable the system 1 to be carried easily and for the system 1to be positioned unobtrusively at a convenient location, such asadjacent an entrance door of a building. The portable configuration ofthe system 1 of some arrangements enables the system 1 to be carriedeasily to a location where there is a need for infectious diseasescreening. In some arrangements, the system 1 is configured to bepowered by a battery or another low power source of electricity so thatthe system 1 can be used at a remote location, without the need formains electricity. In other arrangements, the system 1 comprises a powersource input to be connected to mains electricity to power the system 1and/or to charge a battery within the system 1.

The system 1 comprises a support platform 8 which is provided at thebase of the housing 3. The support platform 8 comprises a surface forcarrying the assay device 2. The support platform 8 comprises aplurality of guide members 9 which are located around the supportplatform 8 to guide the assay device 2 into a predetermined positionwhen the assay device 2 is inserted into the system 1. In thisarrangement, the support platform 8 is provided with a central aperture10 which is positioned beneath the assay device 2 when the assay device2 is carried by the support platform 8.

Referring now to FIG. 2 of the accompanying drawings, the assay device 2comprises a base 11 which, in this arrangement, comprises an enlargedlower end in order to provide stability to the assay device 2 when theassay device 2 is resting on the base 11. The assay device 2 furthercomprises an assay device housing 12 which houses the internalcomponents of the assay device 2, which are described in more detailbelow. The assay device housing 12 comprises an upper end 13 which isremote from the base 11 and which is configured to be opened to provideaccess to within the assay device 2. A cover 14 is movably mounted tothe assay device housing 12 to at least partly cover the upper end 13.The cover 14 comprises a central aperture 15. The cover 14 will bedescribed in more detail below.

The assay device 2 comprises a PCR apparatus 16 which protrudes from oneside of the assay device 2. The PCR apparatus 16 will be described inmore detail below.

Referring now to FIG. 3 of the accompanying drawings, when the assaydevice 2 is inserted into the system 1, the assay device 2 is guidedinto the predetermined position on the support platform 8 such that thePCR apparatus 16 is at least partly received within a heating recess ofa heating apparatus 17, which is described in detail below.

The assay device 2 sits beneath a drive arrangement 18 which forms partof the system 1. In this arrangement, the drive arrangement 18 comprisesa drive element in the form of a plunger 19 which is configured to bemoved by the drive arrangement 18 outwardly from the drive arrangement18 so that a tip 20 of the plunger 19 moves through the aperture 15 inthe cover 14 of the assay device 2 along the direction generallyindicated by arrow 21 to engage a piston 22 within the assay device 2.The system 1 is configured to extend and retract the plunger 19 in orderto move the piston element 22 during the operation of the system 1.

The system 1 comprises a controller 23 which incorporates a computingdevice, such as a microprocessor, and a memory. The controller 23 isconfigured to control the operation of the system 1 as described below.

Referring now to FIGS. 4-6 of the accompanying drawings, the assaydevice 2 comprises a body portion 24 which is elongate and which definesat least one internal chamber. In this arrangement, the body portion 24has sides which are defined by eight generally planar surfaces which arearranged such that the body portion 24 has an octagonal cross-section.It is, however, to be appreciated that other arrangements incorporate abody portion having a different shape and different cross-section.

In this arrangement, the body portion 24 defines a plurality of internalchambers. In this arrangement, the body portion 24 defines six internalchambers; a sample chamber 25, a wash chamber 26, a lysing agent chamber27, a liquid reagent chamber 28, a dry reagent chamber 29 and a wastechamber 30. The body portion 24 is also provided with a central aperture31.

The number of chambers within the assay device can vary in differentarrangements from 1 to as many as 10. In an arrangement for anSARS-CoV-2 assay, the assay device 2 comprises six chambers.

One end of the body portion 24 is provided with a protrusion 32, asshown in FIG. 5. The protrusion 32 is provided with a plurality ofapertures 33, as shown in FIG. 6. Each aperture 33 provides a fluidcommunication path with a respective one of the chambers 25-30.

Referring now to FIG. 7 of the accompanying drawings, the assay device 2comprises a transfer apparatus 34 which is movably mounted to the bodyportion 24. The transfer apparatus 34 comprises a plunger column 35which defines an elongate transfer chamber 36. In this arrangement, theplunger column 35 is an elongate and generally cylindrical column whichis configured to be at least partly received within the central aperture31 of the assay device body 24.

The plunger column 35 is the central part of the assay device 2. It isalso how the liquid contained in the assay device 2 is moved andmanipulated to and from the various chambers as it goes through all thestages of preparation for PCR. The transfer chamber 36 contains a rubberplunger tip that connects to a plunger arm contained within the housingof the system 1. Liquid is drawn into the transfer chamber 36 vianegative pressure before being forced out of the transfer chamber 36towards its destination chamber via positive pressure.

The transfer apparatus 34 comprises an enlarged end 37. In thisarrangement, the enlarged end 37 is generally cylindrical and isprovided with a drive formation in the form of teeth 38 which areprovided at spaced apart positions around the enlarged end 37. The teeth38 are configured to engage a corresponding drive formation on thesystem 1 such that rotation of the corresponding drive formation of thesystem 1 rotates the transfer apparatus 34. The movement of the transferapparatus is controlled by a motor contained within the housing of thesystem 1. The motor is a brushless DC motor, a stepper motor or any sortof electronically driven motor.

Referring now to FIGS. 8 and 9 of the accompanying drawings, thetransfer apparatus 34 comprises a moveable flow path 39 which is definedby internal passages within the enlarged end 37. The moveable flow path39 is configured to move with the transfer apparatus 34 relative to theassay device body 24. The transfer apparatus 34 is provided with flowapertures 40, 41 which are fluidly coupled to the moveable flow path 39.The flow apertures 40, 41 are positioned such that the flow apertures40, 41 are selectively aligned with the apertures 33 on the assay devicebody 24 in order to selectively fluidly couple each respective chamber25-30 to the moveable flow path 39 depending on the position of thetransfer apparatus 34 relative to the assay device body 24.

One of the flow apertures 40 is fluidly coupled with the transferchamber 36 to permit fluid to flow into or out from the transfer chamber36 when the piston 22 is moved along at least part of the length of thetransfer chamber 36 due to the positive or negative pressure producedwithin the transfer chamber 36 as a result of the movement of the piston22.

The transfer apparatus 34 comprises a filtration arrangement 42 which isprovided within the enlarged end 37 such that fluid flowing along themoveable flow path 39 passes through the filtration arrangement 42. Inthis arrangement, the filtration arrangement 42 comprises an array offilters, gaskets and microbeads designed to separate larger pollutantsfrom the cells contained in the sample and trap the cells within a“lysing area”.

Referring to FIG. 10 of the accompanying drawings, the filtrationarrangement 42 comprises at least one filter element. In thisarrangement, the filtration arrangement 42 comprises a first filterelement 43 which is provided with pores of between 2 μm and 30 μm indiameter designed to filter out pollutants such as hair or dust. In thisarrangement, the filtration arrangement 42 comprises a second filterelement 44 which is superimposed on the first filter element 33. Thesecond filter element 44 is provided with pores of between 0.1 μm and 5μm in diameter where the pore size is selected to be slightly smallerthan the average size of the target cells so they are unable to passthrough the second filter element 44.

In this arrangement, the filtration arrangement 42 comprises gaskets45-47 which provide seals around the filter elements 42, 43. In thisarrangement, a larger gasket (approximately 200 μm thick) is providedbetween the first and second filter elements 43, 44 to create spacebetween the first and second filter for the lysing area.

In this arrangement, the filtration arrangement 42 comprises a pluralityof beads B which are retained between the first filter element 43 andthe second filter 44. In some arrangements, the beads B are microbeadshaving a diameter of approximately 100 microns. In some arrangements,approximately half of the beads B are buoyant so they collect near thetop of the filter arrangement 42 during sonication and the other halfare designed to not be buoyant and collect near the bottom of the filterarrangement 42. Between the two types of beads, a majority of the lysingarea will be filled with microbeads that help disrupt cell membranesduring sonication.

Referring now to FIG. 11 of the accompanying drawings, the transferapparatus 34 comprises a sonication chamber 48 which is positionedadjacent to the filtration arrangement 42 and which is fluidly coupledto the moveable flow path 39. In some arrangements, the sonicationchamber 48 has a volume of between 100 μl to 1000 μl. In somearrangements, the inlet to the sonication chamber 48 is positioned at alevel below the outlet of the sonication chamber 48, when the assaydevice 2 is standing upright, to allow liquid to flow from low to highand to let any air bubbles escape in the process.

The filtration arrangement 42 is provided within the sonication chamberand an ultrasonic transducer 49 is provided at the one end of thesonication chamber 48. In some arrangements, the filtration arrangement42 separates the inlet area of the sonication chamber 48 from the outletarea of the sonication chamber 48, substantially between on half or onequarter of the distance between the inlet and the outlet of thesonication chamber 48.

The ultrasonic transducer 49 is coupled electrically to the controller23 of the system 1 when the assay device 2 is inserted into the system1. The ultrasonic transducer 49 is configured to be controlled by thecontroller 23. The controller 23 comprises a processor configured tocontrol at least one process of the system and a memory, the memorystoring executable instructions which, when executed by the processor,cause the processor to provide an output to perform the at least oneprocess. The memory of the controller 23 stores executable instructionswhich, when executed by the processor, cause the processor to controlthe ultrasonic transducer 49 to oscillate at a selected frequency inorder to lyse cell within the sonication chamber 48 to release nucleicacid (DNA/RNA) from the cells.

In some arrangements, the ultrasonic transducer 49 is at least partly ofa compound comprising lead, zirconium and titanium. The compound of theultrasonic transducer 49 is selected to provide the ultrasonictransducer 49 with the properties for it to oscillate at a frequency of2.8 MHz to 3.2 MHz. This frequency range is the preferred frequencyrange for the ultrasonic transducer 49 to produce ultrasonic waves whichlyse or rupture cells.

In some arrangements, the ultrasonic transducer 49 comprises a firstelectrode on an upper side and a second electrode on a lower side whichis on the opposing side of the ultrasonic transducer 49. In somearrangements, the first electrode and the second electrode comprisesilver, for instance in the form of silver stamp paint. In somearrangements, the capacitance between the first electrode and the secondelectrode is 800 pF to 1300 pF.

In some arrangements, the first electrode on the upper side of theultrasonic transducer 49 is at least partly covered with a glasscoating. The glass coating minimizes or prevents possible contaminationof liquid within the sonication chamber 48 by the material of the firstelectrode. The glass coating also minimizes or prevents erosion of thesilver of the first electrode, for instance due to cavitation bubblecollapse caused by ultrasonic waves travelling through liquid within thesonication chamber 48 when the system is in use.

The first and second electrodes of the ultrasonic transducer 49 areconnected electrically to respective first and second electricalterminals of the controller 23.

In some arrangements, the controller 23 comprises an AC driver. The ACdriver generates an AC drive signal at a predetermined frequency andoutputs the AC drive signal to drive the ultrasonic transducer 49. TheAC driver comprises a circuit incorporating electronic components whichare connected to generate an AC drive signal from power received from apower source. In some arrangements, the AC driver comprises a H-bridgecircuit. In some arrangements, the H-bridge circuit comprises fourMOSFETs which are connected to convert a direct current into analternating current at high frequency (e.g. a frequency in the range 2.8MHz to 3.2 MHz).

In some arrangements, the controller 23 comprises an active powermonitor. The active power monitor comprises an electronic circuit whichmonitors the active power used by the ultrasonic transducer 49 when theultrasonic transducer 49 is driven by the AC drive signal. The activepower monitor provides a monitoring signal which is indicative of anactive power used by the ultrasonic transducer 49. In some arrangements,the active power monitor comprises a current sensor which senses a drivecurrent of the AC drive signal driving the ultrasonic transducer 49 andprovides a monitoring signal which is indicative of the sensed drivecurrent.

The processor of the controller 23 controls the AC driver and receivesthe monitoring signal from the active power monitor.

In some arrangements, the controller 23 comprises a frequency controllerwhich is implemented in the executable code stored in the memory which,when executed by the processor, cause the processor to perform at leastone function of the frequency controller.

The memory of the controller 23 stores executable instructions which,when executed by the processor, cause the processor to control theultrasonic transducer 49 to oscillate at a plurality of frequencieswithin a predetermined sweep frequency range and to select a drivefrequency for the ultrasonic transducer 49 which is between a firstpredetermined frequency and a second predetermined frequency for lysingcells within the sonication chamber 48.

In some arrangements, the frequency will be determined by the type ofcells that are being lysed as some cells may require differentfrequencies due to their physical characteristics (size, shape, presenceof cell wall, etc.).

There is an optimum frequency or frequency range for lysing cells withinthe sonication chamber. The optimum frequency or frequency range willdepend on at least the following four parameters;

1. Transducer Manufacturing Processes

In some arrangements, the ultrasonic transducer 49 comprises apiezoelectric ceramic. The piezoelectric ceramic is manufactured bymixing compounds to make a ceramic dough and this mixing process may notbe consistent throughout production. This inconsistency can give rise toa range of different resonant frequencies of the cured piezoelectricceramic.

If the resonant frequency of the piezoelectric ceramic does notcorrespond to the required frequency of operation, the process of lysingcells is not optimal. Even a slight offset in the resonant frequency ofthe piezoelectric ceramic is enough to impact the lysing process,meaning that the system will not function optimally.

2. Load on Transducer

During operation, any changes in the load on the ultrasonic transducer49 will inhibit the overall displacement of the oscillation of theultrasonic transducer 49. To achieve optimal displacement of theoscillation of the ultrasonic transducer 49, the drive frequency must beadjusted to enable the controller 23 to provide adequate power formaximum displacement.

The types of loads that can affect the efficiency of the ultrasonictransducer 49 can include the amount of liquid on the transducer (i.e.the amount of liquid within the sonication chamber 48).

3. Temperature

Ultrasonic oscillations of the ultrasonic transducer 49 are partiallydamped by its assembly in the assay device 2. This dampening of theoscillations can cause a rise in local temperatures on and around theultrasonic transducer 49.

An increase in temperature affects the oscillation of the ultrasonictransducer 49 due to changes in the molecular behavior of the ultrasonictransducer 49. An increase in the temperature means more energy to themolecules of the ceramic, which temporarily affects its crystallinestructure. Although the effect is reversed as the temperature reduces, amodulation in supplied frequency is required to maintain optimaloscillation.

An increase in temperature also reduces the viscosity of the solutionwithin the sonication chamber 48, which may require an alteration to thedrive frequency to optimize lysis of cells within the sonication chamber48.

4. Distance to Power Source

The oscillation frequency of the ultrasonic transducer 49 can changedepending on the wire-lengths between the ultrasonic transducer 49 andthe oscillator-driver. The frequency of the electronic circuit isinversely proportional to the distance between the ultrasonic transducer49 and the controller 23.

Although the distance parameter is primarily fixed in this arrangement,it can vary during the manufacturing process of the system 1. Therefore,it is desirable to modify the drive frequency of the ultrasonictransducer 49 to compensate for the variations and optimize theefficiency of the system.

An ultrasonic transducer 49 can be modelled as an RLC circuit in anelectronic circuit, as shown in FIG. 12. The four parameters describedabove may be modelled as alterations to the overall inductance,capacitance, and/or resistance of the RLC circuit, changing theresonance frequency range supplied to the transducer. As the frequencyof the circuit increases to around the resonance point of thetransducer, the log Impedance of the overall circuit dips to a minimumand then rises to a maximum before settling to a median range.

FIG. 13 shows a generic graph explaining the change in overall impedancewith increase in frequency in the RLC circuit. FIG. 14 shows how apiezoelectric transducer acts as a capacitor in a first capacitiveregion at frequencies below a first predetermined frequency f_(s) and ina second capacitive region at frequencies above a second predeterminedfrequency f_(p). The piezoelectric transducer acts as an inductor in aninductive region at frequencies between the first and secondpredetermined frequencies f_(s), f_(p). In order to maintain optimaloscillation of the transducer and hence maximum efficiency, the currentflowing through the transducer must be maintained at a frequency withinthe inductive region.

The memory of the controller 23 stores executable instructions which,when executed by the processor, cause the processor to maintain thefrequency of oscillation of the ultrasonic transducer 49 within theinductive region, in order to maximize the efficiency of the lysis ofcells within the sonication chamber 48.

The memory of the controller 23 stores executable instructions which,when executed by the processor, cause the processor to perform a sweepoperation in which the controller 23 drives the transducer atfrequencies which track progressively across a predetermined sweepfrequency range. In other words, the driver apparatus 2 drives thetransducer at a plurality of different frequencies across thepredetermined sweep frequency range. For instance at frequencies whichincrement by a predetermined frequency from one end of the sweepfrequency range to the other end of the sweep frequency range.

In some arrangements, as the controller 23 performs the sweep, thecontroller 23 monitors an Analog-to-Digital Conversion (ADC) value of anAnalog-to-Digital converter which is provided within the controller 23and coupled to the ultrasonic transducer 49. In some arrangements theADC value is a parameter of the ADC which is proportional to the voltageacross the ultrasonic transducer 49. In other arrangements, the ADCvalue is a parameter of the ADC which is proportional to the currentflowing through the ultrasonic transducer 49.

During the sweep operation, the controller 23 locates the inductiveregion of the frequency for the transducer. Once the controller 23 hasidentified the inductive region, the controller 23 records the ADC valueand locks the drive frequency of the transducer at a frequency withinthe inductive region (i.e. between the first and second predeterminedfrequencies f_(s), f_(p)) in order to optimize the operation of theultrasonic transducer 49. When the drive frequency is locked within theinductive region, the electro-mechanical coupling factor of thetransducer is maximized, thereby maximizing the operation of theultrasonic transducer 49.

In some arrangements, the controller 23 determines the active powerbeing used by the ultrasonic transducer 49 by monitoring the currentflowing through the transducer 49. The active power is the real or truepower which is dissipated by the ultrasonic transducer 49.

Ultrasonic (piezoelectric) transducer mechanical deformation is linkedto the AC Voltage amplitude that is applied to it, and in order toguarantee optimal functioning and delivery of the system, the maximumdeformation must be supplied to the ultrasonic transducer all the time.By Pulse Width Modulation (PWM) of the AC voltage applied to theultrasonic transducer, the mechanical amplitude of the vibration remainsthe same. In some arrangements, the system actively adjusts the dutycycle of the AC voltage waveform to maximize deformation of theultrasonic transducer in order to guarantee optimal functioning anddelivery of the system.

One approach involves modifying the AC voltage applied to the ultrasonictransducer via the use of a Digital to Analog Converter (DAC), Theenergy transmitted to the ultrasonic transducer would be reduced but sowould the mechanical deformation which as a result does not producemaximum deformation. The RMS voltage applied to the ultrasonictransducer would be the same with effective Duty Cycle modulation aswith Voltage modulation, but the active power transferred to theultrasonic transducer would degrade. Indeed, given the formula below:

Active Power displayed to the ultrasonic transducer being:

${{Pa} = {\frac{2\sqrt{2}}{\pi}{Irms}*{Vrms}*{\cos\varphi}}},$

Where

φ is the shift in phase between current and voltageI_(rms) is the root mean square CurrentV_(rms) is the root mean square Voltage.

When considering the first harmonic, Irms is a function of the realvoltage amplitude applied to the ultrasonic transducer, as the pulsewidth modulation alters the duration of voltage supplied to theultrasonic transducer, controlling Irms.

In this arrangement, the memory of the controller 23 stores instructionswhich, when executed by the processor of the controller 23, cause theprocessor to:

-   -   A. control the AC driver of the controller 23 to output an AC        drive signal to the ultrasonic transducer 49 at a predetermined        sweep frequency;    -   B. calculate the active power being used by the ultrasonic        transducer 49 based on the monitoring signal;    -   C. control the AC driver to modulate the AC drive signal to        maximize the active power being used by the ultrasonic        transducer 49;    -   D. store a record in the memory of the maximum active power used        by the ultrasonic transducer 49 and the sweep frequency of the        AC drive signal;    -   E. repeat steps A-D for a predetermined number of iterations        with the sweep frequency incrementing with each iteration such        that, after the predetermined number of iterations has occurred,        the sweep frequency has been incremented from a start sweep        frequency to an end sweep frequency;    -   F. identify from the records stored in the memory the optimum        frequency for the AC drive signal which is the sweep frequency        of the AC drive signal at which a maximum active power is used        by the ultrasonic transducer 49; and    -   G. control the AC driver to output an AC drive signal to the        ultrasonic transducer 49 at the optimum frequency.

In some arrangements, the start sweep frequency is 2800 kHz and the endsweep frequency is 3200 kHz. In other arrangements, the start sweepfrequency and the end sweep frequency are lower and upper frequencies ofa frequency range within the range of 2800 kHz to 3200 kHz.

In some arrangements, the processor controls the AC driver to output anAC drive signal to the ultrasonic transducer 49 at frequency which isshifted by between 1-10% of the optimum frequency. In thesearrangements, the frequency shift is used to prolong the life of theultrasonic transducer 49 by minimizing potential damage caused to theultrasonic transducer 49 when the ultrasonic transducer 49 is drivencontinuously at the optimum drive frequency which produces maximumdisplacement.

In some arrangements, the AC driver modulates the AC drive signal bypulse width modulation to maximize the active power being used by theultrasonic transducer 49.

In some arrangements, the processor 40 controls the AC driver toalternately output an AC drive signal to the ultrasonic transducer 49 atthe optimum frequency for a first predetermined length of time and tonot output an AC drive signal to the ultrasonic transducer 49 for asecond predetermined length of time. This alternate activation anddeactivation of the ultrasonic transducer 49 has been found to optimizethe process of lysing cells in a sample within the sonication chamber48.

In some arrangements, in order to ensure optimal operation of theultrasonic transducer 49, the controller 23 operates in a recursivemode. When the controller 23 operates in the recursive mode, thecontroller 23 runs the sweep of frequencies in steps A-D periodicallyduring the operation of the system.

In some arrangements, the AC driver of the controller 23 is configuredto alternately output the AC drive signal and to not output the AC drivesignal according to an operating mode. The timings of twelve operatingmodes of some arrangements are shown in Table 1 below.

TABLE 1 First Second predetermined predetermined Operating length oftime length of time mode (seconds) (seconds) 1 4 2 2 3 2 3 2 2 4 1 2 5 11 6 2 1 7 3 1 8 4 1 9 4 3 10 3 3 11 2 3 12 1 3

In some arrangements, the memory of the controller 23 stores executableinstructions which, when executed by the processor, cause the processorto perform the sweep operation to locate the inductive region each timethe oscillation is started or re-started. In these arrangements, thememory of the controller 23 stores executable instructions which, whenexecuted by the processor, cause the processor to lock the drivefrequency at a new frequency within the inductive region each time theoscillation is started and thereby compensate for any changes in theparameters that affect the efficiency of operation of the ultrasonictransducer 49.

In some arrangements, in order to ensure optimal operation of theultrasonic transducer 49, the controller 23 operates in a recursivemode. When the controller 23 operates in the recursive mode, thecontroller 23 runs the sweep of frequencies periodically during theoperation of the system and monitors the ADC value to determine if theADC value is above a predetermined threshold which is indicative ofoptimal oscillation of the operation of the ultrasonic transducer 49.

In some arrangements, the controller 23 runs the sweep operation whilethe system is in the process of lysing cells in case the controller 23is able to identify a possible better frequency for the ultrasonictransducer 49 which maximizes displacement of the ultrasonic transducer49. If the controller 23 identifies a better frequency, the controller23 locks the drive frequency at the newly identified better frequency inorder to maintain optimal operation of the ultrasonic transducer 49.

FIG. 15 shows a flow diagram of the operation of the controller 23 ofsome arrangements.

Referring now to FIGS. 16 and 17 of the accompanying drawings, the lid14 of the assay device 2 comprises a generally planar cover 50 which isconfigured to close an open end of at least the sample chamber 25 of theassay device body 24. The lid 14 comprises side walls 51 which extendaround the periphery of the cover 50. In this arrangement, an air inletaperture 52 is provided in one of the side walls 51.

In this arrangement, the lid 14 comprises a pivotal mounting arrangement53 for pivotally mounting the lid 14 to the assay device body 24. Inother arrangements, the lid 14 is configured with a different movablemounting arrangement to moveably mount the lid 14 to the assay devicebody 24.

The lid 14 comprises a gas permeable membrane 54 which is superimposedbeneath the lid member 50 around the ends of the side walls 51. The gaspermeable membrane 54 provides a substantially gas tight seal around theside walls 51 and around the central aperture 15 to prevent crosscontamination or accidental spillage. In some arrangements, the gaspermeable membrane 54 is a Gore-Tex™ material.

In use, the air inlet aperture 52 allows air to flow into the lid 14 andfor the air to flow through the gas permeable membrane 54 and into atleast the sample chamber 25 within the assay device body 24.

In other arrangements, the gas permeable membrane 54 may be replacedwith another one-way gas flow member, such as a valve.

Referring now to FIGS. 18-20 of the accompanying drawings, the PCRapparatus 16 of the assay device 2 comprises a fin 55 which is coupledto the assay device body 24 such that the fin 55 protrudes outwardlyfrom the assay device body 24. The fin 55 comprises an enlarged mountingmember 56 which is configured to be connected to the assay device body24. The mounting member 56 is provided with a first aperture 57 and asecond aperture 58 which extend through to the fin 55 such that theapertures 57, 58 are in fluid communication with a PCR chamber 59 whichis defined within the fin 55. In this arrangement, the fin 55 furthercomprises a plurality of internal chambers 60 in a central portion 61which partly surrounds the PCR chamber 59.

The fin 55 is generally rectangular with angled ends 62, 63 whichconverge to a point 64, In use, after the sample passes through both thereagent chambers of the assay device 2, it is pushed into the PCR fin 55which contains the PCR chamber 59.

In some arrangements, the reagents selected for the PCR process arechosen in order to facilitate an extreme rRT-PCR process as well asallow for temperature monitoring via fluorescence. In some arrangements,the reagent formula consists of or comprises: 5 μM of each forward andreverse primer (6 total primers, 2 sets for detecting SARS-COV-2 and 1set to serve as a control for a successful PCR reaction), IX LCGreen+dye, 0.2 μM of each deoxynucleoside triphosphate (dNTP): dATP, dTTP,dGTP, dCTP, 50 mM Tris, 1.65 μM KlenTaq, 25 ng/μL BSA, 1.25 U/μL MaloneMurine leukemia virus reverse transcriptase (MMLV), 7.4 mM MgCl₂, andsulforhodamine B.

Referring now to FIGS. 21 and 22 of the accompanying drawings, the fin55 of the PCR apparatus 16 is configured to be at least partly receivedwithin the heating apparatus 17.

In this arrangement, the heating apparatus 17 comprises two generallycircular planar discs 65, 66 which are spaced apart from one another androtatably mounted to a pivot member 67. A heating recess 68 is definedby a part of the space between the discs 65, 66.

In this arrangement, one of the discs 65 is a movable support elementwhich carries a first heating element 69 and a second heating element70, as shown in FIG. 23. The first and second heating elements 69, 70are spaced apart from one another on either side of the disc 65.

The heating apparatus 17 further comprises a motor which is configuredto move the disc 65 to rotate about the pivot member 67 so that the disc65 moves between a first position in which the first heating element 69is positioned closer to the heating recess 68 than the second heatingelement 70 and a second position in which the second heating element 70is positioned closer to the heating recess 68 than the first heatingelement 69. The motor is coupled electrically to the controller 23 sothat the controller 23 can control the motor to move the disc 65cyclically between the first position and the second position.

In some arrangements, the heating apparatus 17 comprises a temperaturesensor which is configured to sense the temperature of a liquid withinthe PCR apparatus positioned within the heating recess 68 and the systemis configured to control the movement of the first and second heatingelements in response to the sensed temperature.

Referring now to FIG. 24 of the accompanying drawings, the system 1comprises an infectious disease detection arrangement in the form of afluorescence detection arrangement 70 which comprises a generally planarsupport member 71 which is provided with an aperture 72 through whichthe pivot member 67 extends. The fluorescence detection arrangementcomprises a first triangular portion 73 and a second triangular portion74 and an indented portion 75. The planar body 71 and the triangularportions 73, 74 are positioned in the space between the discs 65, 66 ofthe heating apparatus.

The indented portion 75 is shaped to receive the pointed end of the fin55 of the PCR apparatus 16.

The detection apparatus 70 is provided with a plurality of lightemitters 76 along one edge of the recessed portion 75 and a plurality ofphoto receptors 77 along another edge of the recessed portion 75. Inthis arrangement, there are four light emitters in the form of four LEDswhich are each configured to transmit light at a different wavelengthand there are four photo detectors 77 which are each configured todetect light at a different wavelength. However, in other arrangements,there are a different number of light emitters and photo detectors.

The detection apparatus 70 is, in some arrangements, configured todetect the fluorescence emitted from the LCGreen+ and sulforhodamine Bdyes to monitor PCR, melting curves and temperature changes.

In some arrangements, the detection apparatus is a SARS-CoV-2 virusdetection apparatus detects a presence of the SARS-CoV-2 virus thatcauses COVID-19 disease.

Result Reporting

In some arrangements, the system 1 comprises a display, such as an LCDmonitor, on the exterior of the housing 3. After the information fromthe system has been processed by the controller 23, the result of thetest will be displayed on the display. The four possible results of theassay are as follows: Positive, Negative, Inconclusive, or Invalid. Inthe case of a COVID-19 test, the criteria for the four results are shownin Table 2 below.

TABLE 2 COVID COVID RNAse P Gene1 Gene2 ‘control’ Result Report + + +/−2019-nCOV Positive detected One of two is + +/− InconclusiveInconclusive − − + 2019-nCOV not Negative detected − − − Invalid resultInvalid

SARS-COV-2 Example

The operation of a system of some arrangements will now be described fora SARS-COV-2 assay.

In the assay device 2, the first chamber is the sample chamber intowhich a user adds a target sample to be screened. In some arrangements,the target sample is a saliva sample or a sputum sample. In otherarrangements, the target sample is collected from a user by anasopharyngeal swab or an oropharyngeal swab. In further arrangements,the target sample is a blood sample.

In some arrangements, the target sample is between 1 ml to 5 ml involume. The sample, after being collected from the patient, is placedinto an elution buffer prior to being added to the sample chamber. Insome arrangements, the elution buffer comprises: 1M Imidazole solution,1M Tris, 0.5M EDTA, Milli-Q or Deionized water.

The next chamber is the wash chamber. In some arrangements, the washchamber contains an excess amount (3 ml to 5 ml) of an elution buffer asmentioned above. The wash buffer is used to wash the sample to removeany potential contaminants.

The next chamber is the lysing agent chamber. In some arrangements, thelysing agent chamber contains a mixture of chemicals to assist in thecell lysing step of the assay. In some arrangements, the lysing agentcomprises a formulation, including, but not limited to the followingthree formulations:

Lysis Formula #1:

-   -   10 mM Tris    -   0.25% Igepal    -   CA-630    -   150 mM NaCl

Lysis Formula #2:

-   -   10 mM Tris-HCl    -   10 mM NaCl    -   10 mM EDTA    -   0.5% Triton-X100

Lysis Formula #3:

-   -   0.1M LiCl    -   0.1M Tris-HCl    -   1% SDS    -   10 mm EDTA

The next chamber is the liquid reagent mixing chamber. Once the samplehas been sonicated and cell lysis has occurred, the freed nucleic acidis then pushed to the liquid reagent mixing chamber via pressure fromthe plunger column. The liquid reagent chamber contains theliquid-stable components of the rRT-PCR reagent mixture. Examplecomponents held in this chamber are, in some arrangements: Tris, IXLCGreen Dye, free nucleotides, MgCl₂ or sulforhodamine B.

The next chamber is the lyophilized reagent mixing chamber. This chambercontains a freeze-dried or lyophilized form of reagents that are notable to be stored for long periods in a liquid or hydrated state such asproteins. Example components that would be lyophilized for long-termstorage in the assay device are, in some arrangements: primers,polymerases, reverse transcriptase or bovine serum albumin (BSA).

The next chamber is the PCR chamber, this chamber is located external tothe main section of the pod in the PCR fin. This chamber is where thefinal mixed PCR solution (containing the freed nucleic acid from theinitial sample and all of the PCR reagents) is sent prior to the rRT-PCRprocess.

The final chamber is the waste chamber. This chamber holds all thediscarded components throughout the cycles of the assay device. Forexample, when the wash solution is pushed through the sonicationchamber, the solution is sent directly to the waste chamber upon exitingthe sonication chamber. The volume of this chamber should be at minimumthe total volume of all the liquid in the pod, plus the volume of thesample added.

PCR Methods

The method of some arrangements performs rRT-PCR for rapid detection andconfirmation of the presence of SARS-COV-2 in a sample. In order tocontrol the heating and cooling process necessary for a RT-PCR reactionto occur, the system of some arrangements uses the heating apparatus 17as a thermal cycler with dual heating elements that provide thenecessary temperature cycles.

The discs 65, 66 of the heating apparatus 17 rotate rapidly during theextreme rRT-PCR cycling to apply different heat levels to heat the PCRchamber to the desired temperatures. Heating elements 69 a, 69 b arelocated on opposite sides of the disc and each occupy an area of aquarter of the surface area of the disc Each heating element 69 a, 69 bis programmed to reach a certain temperature.

The first heating element 69 a heats initially to 45° C., pauses for thereverse transcriptase step, then heats to its PCR temperature of 55° C.The second heating element 69 b heats to 95° C. and is only used duringthe PCR step. The other two sections of the disc 65 serve as insulatingareas between the heating elements 69 a, 69 b.

In some arrangement, the heat cycling occurs as follows: a ramp up to45° C. of the first heating element 69 a while the PCR chamber isexposed to an insulating section of the disc. Once the first heatingelement 69 a reaches 45° C., the disc 65 rotates to expose the PCRchamber to the second heating element 69 b for 2 seconds to allow thereverse transcriptase process to occur, Immediately following that, thefirst heating element heats to 55° C. and the PCR process begins.

In some arrangements, the disc 65 begins to rapidly alternate betweenexposing the PCR chamber to the first and second heating elements forapproximately 30-35 cycles of heating and cooling. After each rotationof the disc 65, the temperature of the liquid in the PCR chamber ismonitored using passive fluorescence detection of the sulforhodamine Bdye.

When the second heating element 69 b is adjacent to the PCR chamber andthe temperature of the liquid within the PCR chamber reaches 95° C., thedisc 65 is triggered to rotate and move first heating element 69 aadjacent to the PCR chamber. When the temperature then drops to 55° C.,the disc 65 rotates back to the second heating element 69 b. Thiscompletes one cycle.

Following the last PCR cycle, the first heating element 69 a is rotatedadjacent to the PCR chamber and begins heating at a rate of 8° C./s to atemperature between 90° C. and 100° C. to allow for the melting analysisto be performed to confirm the presence of specific PCR products.

The system 1 is capable of providing test results within 10 minutes and,in some arrangements, as little as 5 minutes or less. This issignificantly faster than conventional PCR tests and it opens up thepossibility for rapid testing at homes, shops, entertainment venues, aswell as airports, bus and train terminals and other transportfacilities.

The system 1 of some arrangements is highly portable and can be carriedeasily to a location where testing is required. The efficient operationof the system enables the system of some arrangements to be powered by abattery, enabling the system to provide tests at virtually any location.

The foregoing outlines features of several embodiments so that those ofordinary skill in the art may better understand various aspects of thepresent disclosure, Those of ordinary skill in the art should appreciatethat they may readily use the present disclosure as a basis fordesigning or modifying other processes and structures for carrying outthe same purposes and/or achieving the same advantages of variousembodiments introduced herein. Those of ordinary skill in the art shouldalso realize that such equivalent constructions do not depart from thespirit and scope of the present disclosure, and that they may makevarious changes, substitutions, and alterations herein without departingfrom the spirit and scope of the present disclosure.

Although the subject matter has been described in language specific tostructural features or methodological acts, it is to be understood thatthe subject matter of the appended claims is not necessarily limited tothe specific features or acts described above. Rather, the specificfeatures and acts described above are disclosed as example forms ofimplementing at least some of the claims.

Various operations of embodiments are provided herein. The order inwhich some or all of the operations are described should not beconstrued to imply that these operations are necessarily orderdependent. Alternative ordering will be appreciated having the benefitof this description. Further, it will be understood that not alloperations are necessarily present in each embodiment provided herein.Also, it will be understood that not all operations are necessary insome embodiments.

Moreover, “exemplary” is used herein to mean serving as an example,instance, illustration, etc., and not necessarily as advantageous. Asused in this application, “or” is intended to mean an inclusive “or”rather than an exclusive “or”. In addition, “a” and “an” as used in thisapplication and the appended claims are generally be construed to mean“one or more” unless specified otherwise or clear from context to bedirected to a singular form. Also, at least one of A and B and/or thelike generally means A or B or both A and B. Furthermore, to the extentthat “includes”, “having”, “has”, “with”, or variants thereof are used,such terms are intended to be inclusive in a manner similar to the term“comprising”. Also, unless specified otherwise, “first,” “second,” orthe like are not intended to imply a temporal aspect, a spatial aspect,an ordering, etc. Rather, such terms are merely used as identifiers,names, etc, for features, elements, items, etc. For example, a firstelement and a second element generally correspond to element A andelement B or two different or two identical elements or the sameelement.

Also, although the disclosure has been shown and described with respectto one or more implementations, equivalent alterations and modificationswill occur to others of ordinary skill in the art based upon a readingand understanding of this specification and the annexed drawings. Thedisclosure comprises all such modifications and alterations and islimited only by the scope of the following claims. In particular regardto the various functions performed by the above described features(e.g., elements, resources, etc.), the terms used to describe suchfeatures are intended to correspond, unless otherwise indicated, to anyfeatures which performs the specified function of the described features(e.g., that is functionally equivalent), even though not structurallyequivalent to the disclosed structure. In addition, while a particularfeature of the disclosure may have been disclosed with respect to onlyone of several implementations, such feature may be combined with one ormore other features of the other implementations as may be desired andadvantageous for any given or particular application.

Embodiments of the subject matter and the functional operationsdescribed herein can be implemented in digital electronic circuitry, orin computer software, firmware, or hardware, including the structuresdisclosed in this specification and their structural equivalents, or incombinations of one or more of them.

Features of some embodiments are implemented using one or more modulesof computer program instructions encoded on a computer-readable mediumfor execution by, or to control the operation of, a data processingapparatus or a controller. The computer-readable medium can be amanufactured product, such as hard drive in a computer system or anembedded system. The computer-readable medium can be acquired separatelyand later encoded with the one or more modules of computer programinstructions, such as by delivery of the one or more modules of computerprogram instructions over a wired or wireless network. Thecomputer-readable medium can be a machine-readable storage device, amachine-readable storage substrate, a memory device, or a combination ofone or more of them.

The terms “computing device” and “data processing apparatus” encompassall apparatus, devices, and machines for processing data, including byway of example a programmable processor, a computer, or multipleprocessors or computers. The apparatus can include, in addition tohardware, code that creates an execution environment for the computerprogram in question, e.g., code that constitutes processor firmware, aprotocol stack, a database management system, an operating system, aruntime environment, or a combination of one or more of them. Inaddition, the apparatus can employ various different computing modelinfrastructures, such as web services, distributed computing and gridcomputing infrastructures.

The processes and logic flows described in this specification can beperformed by one or more programmable processors executing one or morecomputer programs to perform functions by operating on input data andgenerating output.

As used herein, in some embodiments the term module comprises a memoryand/or a processor configured to control at least one process of asystem or a circuit structure. The memory storing executableinstructions which, when executed by the processor, cause the processorto provide an output to perform the at least one process. Embodiments ofthe memory include non-transitory computer readable media.

Processors suitable for the execution of a computer program include, byway of example, both general and special purpose microprocessors, andany one or more processors of any kind of digital computer. Generally, aprocessor will receive instructions and data from a read-only memory ora random access memory or both. The essential elements of a computer area processor for performing instructions and one or more memory devicesfor storing instructions and data. Generally, a computer will alsoinclude, or be operatively coupled to receive data from or transfer datato, or both, one or more mass storage devices for storing data, e.g.,magnetic, magneto-optical disks, or optical disks. However, a computerneed not have such devices. Devices suitable for storing computerprogram instructions and data include all forms of non-volatile memory,media and memory devices, including by way of example semiconductormemory devices, e.g., EPROM (Erasable Programmable Read-Only Memory),EEPROM (Electrically Erasable Programmable Read-Only Memory), and flashmemory devices; magnetic disks, e.g., internal hard disks or removabledisks; magneto-optical disks; and CD-ROM and DVD-ROM disks.

To provide for interaction with a user, some embodiments are implementedon a computer having a display device, e.g., a CRT (cathode ray tube) orLCD (liquid crystal display) monitor, for displaying information to theuser and a keyboard and a pointing device, e.g., a mouse or a trackball,by which the user can provide input to the computer. Other kinds ofdevices can be used to provide for interaction with a user as well; forexample, feedback provided to the user can be any form of sensoryfeedback, e.g., visual feedback, auditory feedback, or tactile feedback;and input from the user can be received in any form, including acoustic,speech, or tactile input.

In the present specification “comprise” means “includes or consists of”and “comprising” means “including or consisting of”.

The features disclosed in the foregoing description, or the followingclaims, or the accompanying drawings, expressed in their specific formsor in terms of a means for performing the disclosed function, or amethod or process for attaining the disclosed result, as appropriate,may, separately, or in any combination of such features, be utilized forrealizing the invention in diverse forms thereof.

1. A COVID-19 disease screening system comprising: a sonication chamberconfigured to receive a biological sample to be screened for COVID-19disease; an ultrasonic transducer in ultrasonic communication with thesonication chamber, which outputs ultrasonic waves in a frequency rangeof approximately 2800 kHz to approximately 3200 kHz to lyse cells fromthe biological sample within the sonication chamber; a controllercomprising: an AC driver which generates an AC drive signal at afrequency within the frequency range of approximately 2800 kHz toapproximately 3200 kHz and outputs the AC drive signal to drive theultrasonic transducer; an active power monitor which monitors activepower used by the ultrasonic transducer when the ultrasonic transduceris driven by the AC drive signal, wherein the active power monitorprovides a monitoring signal which is indicative of the active powerused by the ultrasonic transducer; a processor which controls the ACdriver and receives the monitoring signal from the active power monitor;and a memory storing instructions which, when executed by the processor,cause the processor to: A. control the AC driver to output the AC drivesignal to the ultrasonic transducer at a frequency with the frequencyrange; B. calculate the active power being used by the ultrasonictransducer based on the monitoring signal; C. control the AC driver tomodulate the AC drive signal to maximize the active power being used bythe ultrasonic transducer; D. store a record in the memory of themaximum active power used by the ultrasonic transducer and the frequencyof the AC drive signal; E. repeat steps A-D for a predetermined numberof iterations with the ultrasonic transducer being driven at a pluralityof different frequencies across the frequency range of approximately2800 kHz to approximately 3200 kHz; F. identify from the records storedin the memory an optimum frequency for the AC drive signal which is thefrequency of the AC drive signal at which the maximum active power isused by the ultrasonic transducer; and G. control the AC driver tooutput the AC drive signal to the ultrasonic transducer at the optimumfrequency; wherein the system further comprises: a Polymerase ChainReaction, “PCR”, apparatus which receives and amplifies DNA from thesample; and a SARS-CoV-2 virus detection apparatus which detects apresence of the SARS-CoV-2 virus that causes COVID-19 disease in theamplified DNA and provides an output which is indicative of whether ornot the SARS-CoV-2 virus detection apparatus detects the presence of theCOVID-19 disease in the amplified DNA.
 2. The COVID-19 disease screeningsystem of claim 1, wherein the active power monitor comprises: a currentsensor which senses a drive current of the AC drive signal driving theultrasonic transducer, wherein the active power monitor provides themonitoring signal which is indicative of the sensed drive current. 3.The COVID-19 disease screening system of claim 1, wherein the memorystores instructions which, when executed by the processor, cause theprocessor to: repeat steps A-D with the frequency being incremented froma start frequency of 2800 kHz to an end frequency of 3200 kHz.
 4. TheCOVID-19 disease screening system of claim 1, wherein the memory storesinstructions which, when executed by the processor, cause the processorto: in step G, control the AC driver to output the AC drive signal tothe ultrasonic transducer at a frequency which is shifted by between1-10% of the optimum frequency.
 5. The COVID-19 disease screening systemof claim 1, wherein the AC driver modulates the AC drive signal by pulsewidth modulation to maximize the active power being used by theultrasonic transducer.
 6. The COVID-19 disease screening system of claim1, wherein the memory stores instructions which, when executed by theprocessor, cause the processor to: control the AC driver to alternatelyoutput the AC drive signal to the ultrasonic transducer at the optimumfrequency for a first predetermined length of time and to not output theAC drive signal to the ultrasonic transducer for a second predeterminedlength of time.
 7. The COVID-19 disease screening system of claim 6,wherein the memory stores instructions which, when executed by theprocessor, cause the processor to: alternately output the AC drivesignal and to not output the AC drive signal according to an operatingmode selected from: First Second predetermined predetermined Operatinglength of time length of time mode (seconds) (seconds) 1 4 2 2 3 2 3 2 24 1 2 5 1 1 6 2 1 7 3 1 8 4 1 9 4 3 10 3 3 11 2 3 12 1 3


8. The COVID-19 disease screening system of claim 1, wherein the systemfurther comprises: a heating apparatus incorporating: a heating recesswhich receives a part of the PCR apparatus; a moveable support element;a first heating element which is carried by the support element; asecond heating element which is carried by the support element at aspaced apart position from the first heating element, wherein thesupport element is moveable between a first position in which the firstheating element is positioned closer to the heating recess than thesecond heating element and a second position in which the second heatingelement is positioned closer to the heating recess than the firstheating element; and a motor which is configured to move the supportelement cyclically between the first position and the second position.9. The COVID-19 disease screening system of claim 8, wherein the heatingapparatus comprises: a temperature sensor which senses the temperatureof a liquid within the PCR apparatus positioned within the heatingrecess, wherein the controller controls the movement of the first andsecond heating elements in response to the sensed temperature.
 10. TheCOVID-19 disease screening system of claim 8, wherein the controllercontrols the first heating element to heat the liquid within the PCRapparatus to substantially 45° C. during a reverse transcriptaseprocess.
 11. The COVID-19 disease screening system of claim 9, wherein,during a PCR process, the controller: controls the first heating elementto heat the liquid within the PCR apparatus to substantially 55° C.,controls the second heating element to heat the liquid within the PCRapparatus to substantially 95° C., and moves the support elementcyclically between the first and second positions such that the firstand second heating elements control the temperature of the liquid withinthe PCR apparatus to cycle between substantially 55° C. andsubstantially 95° C.
 12. The COVID-19 disease screening system of claim1, wherein the system further comprises: a moveable flow path which ismoveable to selectively provide a fluid flow path between a samplechamber, the sonication chamber or a PCR chamber so that at least partof the sample can be transferred successively between the samplechamber, the sonication chamber and the PCR chamber.
 13. The COVID-19disease screening system of claim 12, wherein the system furthercomprises: a filtration arrangement which filters fluid flowing out fromthe moveable flow path, the filtration arrangement comprising a firstfilter element which is provided with pores of between 2 μm and 30 μm indiameter.
 14. The COVID-19 disease screening system of claim 13, whereinthe filtration arrangement comprises a second filter element which issuperimposed on the first filter element, the second filter elementbeing provided with pores of between 0.1 μm and 5 μm in diameter.
 15. ACOVID-19 disease screening method, the method comprising: placing abiological sample to be screened for COVID-19 disease into a sonicationchamber, the sonication chamber comprising an ultrasonic transducerwhich outputs ultrasonic waves in a frequency range of approximately2800 kHz to approximately 3200 kHz to lyse cells from the biologicalsample within the sonication chamber; generating, by an AC driver, an ACdrive signal at a frequency within the frequency range of approximately2800 kHz to approximately 3200 kHz and outputting the AC drive signal tothe ultrasonic transducer to drive the ultrasonic transducer;monitoring, by an active power monitor, active power used by theultrasonic transducer when the ultrasonic transducer is driven by the ACdrive signal, wherein the active power monitor provides a monitoringsignal which is indicative of an active power used by the ultrasonictransducer; and receiving, at a processor, the monitoring signal fromthe active power monitor; wherein the method further comprises: A.controlling, by the processor, the AC driver to output the AC drivesignal to the ultrasonic transducer at a frequency within frequencyrange; B. calculating, by the processor, the active power being used bythe ultrasonic transducer based on the monitoring signal; C.controlling, by the processor, the AC driver to modulate the AC drivesignal to maximize the active power being used by the ultrasonictransducer; D. storing, by the processor, a record in the memory of themaximum active power used by the ultrasonic transducer and the frequencyof the AC drive signal; E. repeating steps A-D for a predeterminednumber of iterations with the ultrasonic transducer being driven at aplurality of different frequencies across the frequency range ofapproximately 2800 kHz to approximately 3200 kHz; F. identifying, by theprocessor, from the records stored in the memory an optimum frequencyfor the AC drive signal which is the sweep frequency of the AC drivesignal at which the maximum active power is used by the ultrasonictransducer; and G. controlling, by the processor, the AC driver tooutput an AC drive signal to the ultrasonic transducer at the optimumfrequency; wherein the method further comprises: receiving andamplifying DNA from the sample at a Polymerase Chain Reaction, “PCR”,apparatus; detecting, at a SARS-CoV-2 virus detection apparatus, apresence of the SARS-CoV-2 virus that causes COVID-19 disease in theamplified DNA; and providing an output which is indicative of whether ornot the SARS-CoV-2 virus detection apparatus detects the presence of theCOVID-19 disease in the amplified DNA.
 16. The COVID-19 diseasescreening method of claim 15, wherein the method further comprises:sensing, by a current sensor, a drive current of the AC drive signaldriving the ultrasonic transducer; and providing, by the active powermonitor, a monitoring signal which is indicative of the sensed drivecurrent.
 17. The COVID-19 disease screening method of claim 15, whereinthe method further comprises: modulating, by the AC driver, the AC drivesignal by pulse width modulation to maximize the active power being usedby the ultrasonic transducer.
 18. The COVID-19 disease screening methodof claim 15, wherein the method further comprises: controlling the ACdriver to alternately output the AC drive signal to the ultrasonictransducer at the optimum frequency for a first predetermined length oftime and to not output the AC drive signal to the ultrasonic transducerfor a second predetermined length of time.
 19. The COVID-19 diseasescreening method of claim 18, wherein the method further comprises:controlling the AC driver to alternately output the AC drive signal andto not output the AC drive signal according to an operating modeselected from: First Second predetermined predetermined Operating lengthof time length of time mode (seconds) (seconds) 1 4 2 2 3 2 3 2 2 4 1 25 1 1 6 2 1 7 3 1 8 4 1 9 4 3 10 3 3 11 2 3 12 1 3


20. An infectious disease screening system comprising: a sonicationchamber configured to receive a biological sample to be screened for aninfectious disease; an ultrasonic transducer in ultrasonic communicationwith the sonication chamber, which outputs ultrasonic waves in afrequency range of approximately 2800 kHz to approximately 3200 kHz tolyse cells from a biological sample within the sonication chamber; acontroller comprising: an AC driver which generates an AC drive signalat a frequency within the frequency range of approximately 2800 kHz toapproximately 3200 kHz and outputs the AC drive signal to drive theultrasonic transducer; an active power monitor which monitors activepower used by the ultrasonic transducer when the ultrasonic transduceris driven by the AC drive signal, wherein the active power monitorprovides a monitoring signal which is indicative of the active powerused by the ultrasonic transducer; a processor which controls the ACdriver and receives the monitoring signal from the active power monitor;and a memory storing instructions which, when executed by the processor,cause the processor to: A. control the AC driver to output the AC drivesignal to the ultrasonic transducer at a frequency within the frequencyrange; B. calculate the active power being used by the ultrasonictransducer based on the monitoring signal; C. control the AC driver tomodulate the AC drive signal to maximize the active power being used bythe ultrasonic transducer; D. store a record in the memory of themaximum active power used by the ultrasonic transducer and the frequencyof the AC drive signal; E. repeat steps A-D for a predetermined numberof iterations with the ultrasonic transducer being driven at a pluralityof different frequencies across the frequency range of approximately2800 kHz to approximately 3200 kHz; F. identify from the records storedin the memory an optimum frequency for the AC drive signal which is thesweep-frequency of the AC drive signal at which the maximum active poweris used by the ultrasonic transducer; and G. control the AC driver tooutput the AC drive signal to the ultrasonic transducer at the optimumfrequency; wherein the system further comprises: a Polymerase ChainReaction, “PCR”, apparatus which receives and amplifies DNA from lysedcells of the biological sample; and an infectious disease detectionapparatus which detects a presence of an infectious disease in theamplified DNA and provides an output which is indicative of whether ornot the infectious disease detection apparatus detects the presence ofan infectious disease in the amplified DNA.